RESUMO
The following paper is the result of a semester-long program evaluation course at Spalding University, located in Louisville, Kentucky. During the course, the students were connected to Bridgehaven, a community based psychiatric rehabilitation and recovery program, also located in Louisville, Kentucky. The researchers of this project studied the long-term effectiveness of its Cognitive Enhancement Therapy (CET) program. Based on the data, the results did not yield significant results. However, this is potentially due to the low sample size and incomplete data set. In lieu of this, the researchers offered some recommendations to improve the collection of client information and possible future research.
Assuntos
Terapia Cognitivo-Comportamental , Estudantes , Humanos , Terapia Cognitivo-Comportamental/métodos , Kentucky , Avaliação de Programas e Projetos de Saúde , CogniçãoRESUMO
BACKGROUND: Southeast Asian populations are increasingly affected by allergic airway diseases. Etiology and specific causes, however, are still unknown. The aim of this study is therefore to identify allergens and risk factors for the high prevalence of allergic airway disease in the tropical urban environment. METHODS: Symptoms of allergic rhinitis (AR), asthma, and allergic dermatitis were recorded in two independent cohorts of 576 and 7373 ethnic Chinese individuals living in Singapore. Reactivity against common allergens was determined by skin prick tests (SPT); specific immunoglobulin E (sIgE) titers against 12 common allergens, as well as total serum IgE (tIgE), were measured in the smaller cohort. RESULTS: Immunoglobulin E sensitization was almost exclusively directed against house dust mite (HDM) allergens. More than 80% of individuals were HDM-sIgE positive. Of these, less than 30% also had sIgE for other allergens, and similarly, few of the HDM-sIgE-negative individuals reacted to other allergens. Titers for HDM-sIgE were 8-30 times higher than other non-HDM allergen titers and correlated directly with total serum tIgE levels. Migrants from nontropical countries typically arrived with low or undetectable HDM-sIgE but developed substantial titers in a time-dependent fashion. Importantly, prolonged stay in Singapore also resulted in the manifestation of AR and asthma symptoms, contributing to some of the highest national prevalence rates worldwide. CONCLUSION: In a tropical urban environment, the allergic response is dominated by a single allergen class. The mono-specific IgE sensitization against HDM translates into increased prevalence of allergic airway diseases, which now impact a large proportion of the population in Singapore.
Assuntos
Alérgenos/imunologia , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/epidemiologia , Hipersensibilidade Respiratória/etiologia , Clima Tropical , População Urbana , Adolescente , Adulto , Animais , Especificidade de Anticorpos , Criança , Estudos de Coortes , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Prevalência , Hipersensibilidade Respiratória/diagnóstico , Fatores de Risco , Testes Cutâneos , Adulto JovemRESUMO
About one third of osteosarcoma patients develop lung metastasis refractory to chemotherapy. Recent studies indicate that biological response modifiers activating the patient's immune system may help controlling minimal residual disease via pathways distinct from those used by cytotoxic drugs, and therefore prove effective against tumor resistance. Muramyl tripeptide phosphatidylethanolamine (MTP-PE) is a synthetic lipophilic glycopeptide capable of activating monocytes and macrophages to a tumoricidal state. When intercalated in multilamellar liposomes (L-MTP-PE) and injected intravenously, it targets lung, liver, and spleen macrophages. Therapeutic activity of L-MTP-PE was demonstrated in several preclinical models of experimental lung metastasis and in clinical trials in dogs with osteosarcoma. Although macrophage activation was shown to be directly involved in the in vivo anti-metastatic activity of this molecule, cytokine and chemokine secretion by activated macrophages could induce recruitment and stimulation of other immune cells, which may in turn indirectly contribute to the anti-tumor effect. L-MTP-PE has undergone clinical development in humans. In early trials, most side effects of L-MTP-PE were minimal. L-MTP-PE showed signs of efficacy in treatment of patients with recurrent osteosarcoma and the encouraging results from phase II studies led to a phase III trial conducted by the Children's Oncology Group in patients with newly diagnosed high-grade osteosarcoma. Patients were treated with or without L-MTP-PE in combination with multi-drug chemotherapy in adjuvant setting; significantly higher overall survival and disease-free survival were observed in the group receiving L-MTP-PE.
Assuntos
Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Ativação de Macrófagos/efeitos dos fármacos , Osteossarcoma/tratamento farmacológico , Fosfatidiletanolaminas/farmacologia , Acetilmuramil-Alanil-Isoglutamina/farmacologia , Animais , Neoplasias Ósseas/patologia , Química Farmacêutica , Ensaios Clínicos como Assunto , Humanos , Osteossarcoma/patologiaRESUMO
We examined the ability of a bispecific mAb reagent, consisting of a mAb specific for the primate erythrocyte complement receptor cross-linked with an anti-bacterial mAb, to target bacteria in the bloodstream in an acute infusion model in monkeys. In vitro studies demonstrated a variable level of complement-mediated binding (immune adherence) of Pseudomonas aeruginosa (strain PAO1) to primate E in serum. In vivo experiments in animals depleted of complement revealed that binding of bacteria to E was <1% before administration of the bispecific reagent, but within 5 min of its infusion, >99% of the bacteria bound to E. In complement-replete monkeys, a variable fraction of infused bacteria bound to E. This finding may have significant implications in the interpretation of animal models and in the understanding of bacteremias in humans. Treatment of these complement-replete monkeys with the bispecific reagent led to >99% binding of bacteria to E. Twenty-four-hour survival studies were conducted; several clinical parameters, including the degree of lung damage, cytokine levels, and liver enzymes in the circulation, indicate that the bispecific mAb reagent provides a degree of protection against the bacterial challenge.
Assuntos
Anticorpos Antibacterianos/sangue , Anticorpos Biespecíficos/sangue , Anticorpos Monoclonais/sangue , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/imunologia , Animais , Proteínas do Sistema Complemento/deficiência , Proteínas do Sistema Complemento/fisiologia , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Eritrócitos/imunologia , Eritrócitos/metabolismo , Eritrócitos/microbiologia , Proteínas de Fluorescência Verde , Reação de Imunoaderência , Inflamação/imunologia , Inflamação/microbiologia , Inflamação/prevenção & controle , Infusões Intravenosas , Proteínas Luminescentes/administração & dosagem , Proteínas Luminescentes/metabolismo , Macaca fascicularis , Macaca mulatta , Polímeros/administração & dosagem , Polímeros/metabolismo , Ligação Proteica/imunologia , Infecções por Pseudomonas/sangue , Pseudomonas aeruginosa/metabolismo , Receptores de Complemento 3b/sangue , Receptores de Complemento 3b/imunologia , Sepse/sangue , Sepse/imunologia , Sepse/microbiologiaRESUMO
PURPOSE: The goal of this research is to determine the feasibility of an immunotherapeutic approach based on the use of monoclonal antibodies (mAb) to target complement activation fragments on opsonized cancer cells. METHODS: We investigated whether treatment of LNCaP and C4-2 human prostate cancer cell lines with normal human serum would allow for deposition of sufficient amounts of the complement-activation protein C3b and its fragments [collectively referred to as C3b(i)] such that these proteins could serve as cancer-cell-associated antigens for targeting by mAb. Radioimmunoassays, flow cytometry, and magnetic purging with specific immunomagnetic beads were used for the analyses. RESULTS: In vitro opsonization of human prostate cancer cells with normal human serum resulted in deposition of C3b(i) in sufficient quantity (approx. 100,000 molecules/cell) for the cells to be targeted in a variety of protocols. We found that 51Cr-labeled and C3b(i)-opsonized cancer cells could be specifically purged at high efficiency (95%-99%) using anti-C3b(i) mAb covalently coupled to magnetic beads. Flow-cytometry experiments indicated that most normal white cells were not removed under similar conditions. Opsonization of cancer cells with sera from men with prostate cancer led to lower levels of cell-associated IgM and, subsequently, lower amounts of C3b(i) deposited than in normal subjects. Prototype experiments suggested that this deficiency could be corrected by addition of IgM from normal donor plasma. CONCLUSION: mAb directed against complement-activation products may provide new opportunities to deliver diagnostic and therapeutic agents selectively to cancer cells and tumor deposits. These opportunities may include ex vivo purging of C3b(i)-opsonized cancer cells prior to autologous bone marrow or stem cell transplantation.
Assuntos
Adenocarcinoma/patologia , Anticorpos Monoclonais/imunologia , Anticorpos Antineoplásicos/imunologia , Antígenos de Neoplasias/imunologia , Complemento C3b/imunologia , Neoplasias da Próstata/patologia , Adenocarcinoma/sangue , Adenocarcinoma/imunologia , Androgênios , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antineoplásicos/uso terapêutico , Especificidade de Anticorpos , Purging da Medula Óssea , Estudos de Viabilidade , Citometria de Fluxo , Humanos , Imunoglobulina M/imunologia , Testes Imunológicos , Separação Imunomagnética , Imunoterapia , Masculino , Neoplasias Hormônio-Dependentes/imunologia , Neoplasias Hormônio-Dependentes/patologia , Proteínas Opsonizantes/sangue , Proteínas Opsonizantes/imunologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/imunologia , Formação de Roseta , Células Tumorais Cultivadas/imunologiaRESUMO
ELISA techniques developed for the veterinary diagnosis of Rabbit Haemorrhagic Disease (RHD) in domestic rabbits were used for studying the epidemiology of RHD in Australian wild rabbits. The combination of ELISA techniques that distinguished IgA, IgG and IgM antibody responses and a longitudinal data set, mainly based on capture-mark-recapture of rabbits, provided a reliable basis for interpreting serology and set the criteria used to classify rabbits' immunological status. Importantly, young with maternal antibodies, immune rabbits and rabbits apparently re-exposed to RHD were readily separated. Three outbreaks of RHD occurred in 1996-7. The timing of RHD outbreaks was mainly driven by recruitment of young rabbits that generally contracted RHD after they lost their maternally derived immunity. Young that lost maternal antibodies in summer were not immediately infected, apparently because transmission of RHDV slows at that time, but contracted RHD in the autumn when conditions were again suitable for disease spread.
Assuntos
Infecções por Caliciviridae/veterinária , Surtos de Doenças/veterinária , Ensaio de Imunoadsorção Enzimática/veterinária , Vírus da Doença Hemorrágica de Coelhos/isolamento & purificação , Coelhos/virologia , Animais , Animais Selvagens , Austrália/epidemiologia , Infecções por Caliciviridae/epidemiologia , Vírus da Doença Hemorrágica de Coelhos/imunologia , Imunoglobulinas/análise , Dinâmica Populacional , Estações do AnoRESUMO
Heteropolymers (HP), bispecific mAbs which bind target pathogens to primate erythrocytes via complement receptor 1, facilitate clearance of pathogens from the bloodstream by targeting them for destruction in the liver without causing lysis or clearance of the erythrocytes. We show that when HP prepared with mouse IgG are intravenously infused into monkeys one or more times prior to exposure to a prototype pathogen, they bind to erythrocytes and remain in the circulation long enough to act as "sentinels," preventing pathogen invasion of the bloodstream. The effectiveness of HP as sentinels is limited both by the monkey's immune response to the HP and, prior to the immune response, by a gradual loss of the HP from monkey erythrocytes over a period of 1 week, and we have investigated possible causes of this HP loss. In overview, our results suggest that HP prepared with mouse IgG are able to effectively function as sentinels for a minimum of 4 days and, after repeat infusion, possibly for up to 2 weeks.
Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Complexo Antígeno-Anticorpo/imunologia , Bacteriófago phi X 174/imunologia , Receptores de Complemento 3b/imunologia , Animais , Haplorrinos , Fragmentos Fc das Imunoglobulinas/imunologia , Infusões Intravenosas , Camundongos , Polímeros , Fatores de TempoRESUMO
Immune complexes (IC) bound to the primate erythrocyte (E) complement receptor (CR1) are cleared from the circulation of primates and localized to the liver. IC can be bound to E CR1 either via C3b opsonization or with cross-linked mAb complexes (heteropolymers, HP) which contain an mAb specific for CR1 and a mAb specific for a prototype pathogen. The long-term goal of our work is to apply the HP to the treatment of human diseases associated with blood-borne pathogens. Therefore we have investigated the feasibility of a non-primate model by studying clearance in mice of bacteriophage phiX174 bound via HP to primate E. E-HP-phiX174 complexes were prepared in vitro and infused into the circulation of mice under conditions allowing short term survival of E in the circulation. By radioimmunoassays and flow cytometry, we found that phiX174 is removed from E and cleared from the circulation coincident with loss of HP and CR1, and that the majority of cleared phiX174 is localized to the liver. Through the use of HP constructed with Fab' fragments, we verified the requirement for the Fc portion of the mAb in clearance; inhibition of C3 activation delayed clearance, suggesting a role for complement. The present findings in the mouse confirm previous observations in the non-human primate model.
Assuntos
Anticorpos Monoclonais/imunologia , Eritrócitos/imunologia , Fígado/imunologia , Receptores de Complemento/imunologia , Animais , Humanos , Fragmentos Fc das Imunoglobulinas/imunologia , Camundongos , Camundongos Endogâmicos BALB CAssuntos
Exposições como Assunto , Hospitais/história , Museus/história , França , História do Século XXRESUMO
Immune complexes (IC) bound to the primate erythrocyte (E) complement receptor (CR1) are cleared from the circulation of primates and localized to phagocytic cells in the liver and spleen without E destruction. IC can be bound to E CRI either via C3b opsonization or with cross-linked mAb complexes (heteropolymers, HP) which contain a mAb specific for CRI and a mAb specific for an antigen. The long-term goal of our work is to apply the HP system to the treatment of human diseases associated with blood-borne pathogens. This review discusses the mechanism by which the E-bound IC are transferred to acceptor cells. Our studies in animal models as well as our in vitro investigations indicate that IC transfer is rapid (usually >90% in 10 min) and does not lead to lysis or phagocytosis of the E. Experiments with specific inhibitors and the use of IC prepared with Fab' fragments suggest that transfer depends mainly upon recognition by Fc receptors on the acceptor cell. Moreover, we find that IC release from the E is associated with a concerted loss of CR1, and is followed by uptake and internalization of the IC by the acceptor cell. We suggest that recognition and binding of the E-bound IC substrates by Fc receptors allows close contact between the E and acceptor cells, which in turn facilitates proteolysis of E CR1, presumably by a macrophage-associated protease. After proteolysis, the released IC are internalized by the macrophages.
Assuntos
Complexo Antígeno-Anticorpo/sangue , Eritrócitos/imunologia , Fagócitos/imunologia , Receptores de Complemento 3b/sangue , Animais , Anticorpos Monoclonais/metabolismo , Complexo Antígeno-Anticorpo/metabolismo , Transporte Biológico Ativo , Plaquetas/imunologia , Complemento C3b/metabolismo , Humanos , Primatas , Receptores de Complemento 3b/metabolismo , Receptores Fc/metabolismoRESUMO
Previous in vitro and in vivo experiments in our laboratory have demonstrated that cross-linked bispecific monoclonal antibody (mAb) complexes (Heteropolymers, HP) facilitate binding of prototype pathogens to primate erythrocytes (E) via the E complement receptor, CR1. These E-bound immune complexes are safely and rapidly cleared from the bloodstream. In order to generate a robust bispecific system for HP-mediated clearance of real pathogens such as Filoviruses, we have developed the necessary methodologies and reagents using both inactivated Marburg virus (iMV) and a recombinant form of its surface envelope glycoprotein (rGP). We identified mAbs which bind rGP in solution phase immunoprecipitation experiments. HP were prepared by chemically cross-linking an anti-CR1 mAb with several of these anti-Marburg virus mAbs and used to facilitate binding of iMV and rGP to monkey and human E. These HP mediate specific and quantitative binding (> or = 90%) of both antigens to monkey and human E. Binding was also demonstrable in an indirect RIA. E with bound Marburg virus were probed with 125I labeled mAbs to the Marburg surface glycoprotein and more than 100 mAbs are bound per E. It should be possible to adapt this general approach to other pathogens, and experiments underway should lead to an in vivo test of HP-mediated clearance of Marburg virus.
Assuntos
Anticorpos Antivirais/metabolismo , Eritrócitos/virologia , Marburgvirus/metabolismo , Receptores de Complemento 3b/metabolismo , Proteínas do Envelope Viral/imunologia , Animais , Anticorpos Monoclonais/metabolismo , Células Cultivadas , Chlorocebus aethiops , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Marburgvirus/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Radioimunoensaio , Células VeroRESUMO
We have prepared cross-linked, bispecific mAb complexes (heteropolymers) that facilitate rapid and quantitative binding of a prototype pathogen, Escherichia coli, to the complement receptor (CR1) on primate erythrocytes. Incubation of the erythrocyte-heteropolymer-E. coli complexes with freshly isolated human mononuclear cells leads to rapid removal of the E. coli from the erythrocytes, and phagocytosis and killing of the bacteria. The erythrocytes are not lysed or phagocytosed during this transfer reaction, but both heteropolymer and CR1 are removed from the erythrocytes along with the E. coli. These findings parallel observations made in previous in vivo experiments in which heteropolymers were used to facilitate clearance of innocuous prototype pathogens in a monkey model. It should now be possible to extend the heteropolymer paradigm to a live pathogen in a primate model.
Assuntos
Anticorpos Biespecíficos/imunologia , Anticorpos Monoclonais/imunologia , Eritrócitos/imunologia , Escherichia coli/imunologia , Monócitos/imunologia , Fagocitose , Receptores de Complemento 3b/fisiologia , Animais , Citocalasina D/farmacologia , Ácido Edético/farmacologia , Humanos , Macaca , CamundongosRESUMO
We used Anger camera imaging in a monkey model to investigate the organ localization of a prototype particulate pathogen, 131I-labeled bacteriophage phi X174, after it was bound to the primate erythrocyte complement receptor and then cleared from the circulation. This 131I-labeled phi X174 was infused into the circulation of an immunized monkey, and the nascently formed immune complexes showed rapid and quantitative binding to erythrocytes via the immune adherence reaction (complement-mediated binding). Alternatively, phi X174 was infused into the circulation of a naive animal, and then cross-linked bispecific mAb complexes (heteropolymers, anti-CR1 x anti-phi X174) were infused into the circulation. The infused heteropolymers also facilitated rapid and quantitative binding of phi X174 to erythrocytes. In both cases, after a short lag period, the erythrocyte-bound phi X174 was rapidly cleared from the circulation, and the vast majority of the radiolabel was cleared to the liver, with a small amount clearing to the spleen. Further liver imaging confirmed that within 24 h most of the bacteriophage previously cleared to the liver via the heteropolymer system was phagocytosed and destroyed. The findings in this model system provide additional evidence for the potential utility of heteropolymers to facilitate the safe and rapid clearance of blood-borne pathogens as a potential treatment for infectious diseases.
Assuntos
Anticorpos Biespecíficos/farmacologia , Anticorpos Monoclonais/farmacologia , Bacteriófago phi X 174/imunologia , Eritrócitos/imunologia , Fígado/imunologia , Fígado/virologia , Animais , Anticorpos Biespecíficos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Anticorpos Antivirais/análise , Bacteriófago phi X 174/metabolismo , Eritrócitos/metabolismo , Eritrócitos/virologia , Reação de Imunoaderência , Fragmentos Fc das Imunoglobulinas/fisiologia , Infusões Intravenosas , Fígado/metabolismo , Macaca , Macaca fascicularis , Modelos Biológicos , Receptores de Complemento 3b/metabolismo , Vírion/imunologia , Vírion/metabolismoRESUMO
A serological survey of 238 rabbits for antirabbit haemorrhagic disease virus (RHDV) antibodies was made in an industrial rabbitry where no signs of the disease had been reported for four years. Seroconversion was repeatedly detected and was due to a calicivirus antigenically related to RHDV but without its pathogenicity. There was a seroprevalence of 33.3 per cent among young animals at weaning at 31 days old, 27.6 per cent at five to seven days after weaning, 56.1 per cent at 13 to 14 days after weaning, 90.3 per cent at 19 to 20 days and 100 per cent at 32 to 33 days after weaning, and all the breeding rabbits were seropositive. In the last group and in the young at weaning, the anti-RHDV antibodies were mainly class IgG, but they were IgM and IgA at 13 to 14 days after weaning. In older fattening rabbits, there was a decrease of IgM and IgA and an increase of IgG confirmed seroconversion without any specific signs of rabbit haemorrhagic disease. On the basis of these results, the probable time of infection of the meat rabbits with this non-pathogenic virus was immediately after weaning.
Assuntos
Anticorpos Antivirais/imunologia , Infecções por Caliciviridae/imunologia , Vírus da Doença Hemorrágica de Coelhos/imunologia , Criação de Animais Domésticos , Animais , Prevalência , Coelhos , SorologiaRESUMO
The primate erythrocyte complement receptor facilitates both the immune adherence reaction and the immune complex clearance properties of primate erythrocytes. These phenomena have been studied for more than 40 years. However, it has only recently become apparent that these characteristics of primate erythrocytes may be useful in the generation of a therapy based on bispecific monoclonal antibodies. Our approach uses bispecific monoclonal antibody constructs (heteropolymers) that promote binding of specific target pathogens to primate erythrocytes via the complement receptor. Once bound to the erythrocytes, the pathogen-heteropolymer complex should be cleared from the circulation, phagocytosed and destroyed in the liver. Results with several prototype target pathogens in monkey models indicate it may be possible to use this technology to develop a robust and general therapy for the treatment of diseases associated with blood-borne pathogens.
Assuntos
Anticorpos Biespecíficos/imunologia , Anticorpos Monoclonais/imunologia , Bacteriófago phi X 174 , Patógenos Transmitidos pelo Sangue , Eritrócitos/imunologia , Receptores de Complemento/imunologia , Animais , Especificidade de Anticorpos , Bacteriófago phi X 174/imunologia , HaplorrinosRESUMO
Cigarette smoking and tobacco use have been the subjects of numerous studies for many years. Smoking has also been associated with periodontal disease. However, no relationship between a reliable biochemical marker and increased severity of the periodontal condition has yet been described. It was thus the aim of this study to apply the measurement of cotinine, the major metabolite of nicotine, as a quantitative method to assess levels of smoking, and to correlate serum levels of cotinine with severity of periodontal disease. The degree of association between smoking and periodontal attachment loss was investigated in a study including 79 patients 25 to 64 years old suffering from periodontitis. Patients were examined and the following parameters recorded: Gingival Assessment (GA), Probing Pocket Depth (PPD), Clinical Attachment Level (CAL), and Bone Crest Height (BCH). In addition, self-reported histories of tobacco use as well as blood samples for quantitative analysis of serum levels of cotinine were taken. The serum samples were analyzed for cotinine content by means of a competitive-inhibition ELISA technique. The differences in mean cotinine levels were statistically significant (p = 0.0001) between smokers and non-smokers, showing no overlap between the groups. Severity of periodontal attachment loss was positively correlated with serum levels of cotinine for both measures of periodontal disease (CAL p = 0.005; BCH p = 0.008). Results from the present study indicate that serum cotinine levels used as a biochemical marker of smoking status are correlated with severity of periodontal attachment loss.
Assuntos
Cotinina/sangue , Perda da Inserção Periodontal/sangue , Fumar/sangue , Adulto , Perda do Osso Alveolar/patologia , Análise de Variância , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Pessoa de Meia-Idade , Perda da Inserção Periodontal/etiologia , Perda da Inserção Periodontal/patologia , Índice Periodontal , Bolsa Periodontal/patologia , Periodontite/sangue , Periodontite/patologia , Análise de Regressão , Reprodutibilidade dos Testes , Fumar/efeitos adversosAssuntos
Hospitais/história , Museus/história , França , História do Século XX , História Moderna 1601-RESUMO
The effect of age on the humoral response to Porphyromonas gingivalis was assessed in groups of adults (25 to 54 years and 55 to 74 years) with periodontal disease and compared with that in age-matched healthy controls. To determine whether there was an antibody response against P. gingivalis, we measured serum antibodies against whole cells of P. gingivalis 381, A7A1-28, and W50. In addition, antibody levels against purified P. gingivalis outer membrane proteins (i.e., the 43-kDa fimbrial protein and a 75-kDa protein) were also evaluated. Elderly subjects showed the same response to P. gingivalis as younger subjects. Immunoglobulin G (IgG) antibodies to both purified proteins were also elevated in both diseased groups as compared with the normal groups. Total serum IgG, IgA, and IgM levels were also determined by an enzyme-linked immunosorbent assay for all four groups. Total serum IgG levels were elevated in older adults with periodontitis and total IgA levels were elevated in both groups of older adults compared with the younger groups of similar disease status. Total serum IgM levels were comparable for the four groups. Antinuclear antibody titers were assessed in the two groups of older adults and were also found to be higher for the group with periodontitis. These studies show that older adults as well as younger adults have markedly elevated specific antibodies of the IgG and IgA classes to antigens of P. gingivalis, a putative pathogen in both groups. Furthermore, older adults with periodontitis have significantly elevated levels of total serum IgG which may possibly be related to higher levels of autoantibodies.